Coronary Artery Disease
A number of factors can foster the development of CAD in ACHD patients. First, congenital coronary artery abnormalities (anomalous origin and/or course) have been described in a variety of congenital heart defects, for example, congenitally corrected transposition of the great arteries. Another rare cause of angina and myocardial ischaemia in patients with Eisenmenger syndrome is an extrinsic compression of the left coronary ostium by a dilated pulmonary artery. Furthermore, manipulation of the coronary arteries can be an unavoidable part of the surgical repair of the congenital heart defect, for example, reimplantation of the coronary arteries during the arterial switch procedure in transposition of the great arteries or during aortic root replacement in Marfan patients. And finally, atherosclerotic disease similar to that found in patients without congenital heart disease can develop in ACHD patients. While a great deal of effort was put into improving surgical techniques to limit the effect of surgical manipulation on the coronary arteries, prevention and treatment of atherosclerotic disease is often not a priority during the care of ACHD patients since the focus is on the treatment of the congenital heart defect and its sequelae itself.
Cardiovascular Risk Factors
The important contribution of traditional cardiovascular risk factors (CVRF) like arterial hypertension and hyperlipidaemia to the development of atherosclerotic disease is well established in patients without congenital heart defects. The prevalence of these CVRF was studied in 141 ACHD patients with concomitant CAD. The majority of patients (82%) had one or more CVRF with systemic arterial hypertension and hyperlipidaemia being the most prevalent (53% and 25%, respectively). A study from Belgium that included 1976 patients with ACHD reported that only around 20% of the patients had a fully heart-healthy lifestyle without any CVRF. Considering that the median age of these patients was only 26 years, these findings are especially alarming. Worryingly, data on cholesterol levels were not available in this study. Therefore, the full picture may be even worse with a much smaller number of patients presenting without any CVRF.
Arterial hypertension is associated with stroke, myocardial infarction, sudden death, heart failure, peripheral artery disease and end-stage renal disease in the general population. Its prevalence in ACHD patients was found to be somewhere between 30% and 50%. This is in a similar range as reported for the general population. Furthermore, some ACHD patients with selected congenital heart defects are even more prone to have a high blood pressure than the general population or patients with other congenital heart defects. This holds especially true for patients with coarctation of the aorta, in whom the prevalence of arterial hypertension was reported to be much higher than in patients with a ventricular septal defect in a recent study (45% vs 16%). In contrast, some patients with complex lesions, for example, with a Fontan circulation, have low blood pressure values due to a chronic impairment in cardiac output.
Data regarding the occurrence of obesity in ACHD patients are inconclusive. While in the already mentioned Belgian study patients with ACHD were more often obese than the general population, a study from the Netherlands reported that the proportion of ACHD patients that were overweight or obese was smaller than in the general population. Nonetheless, 40% of ACHD patients were overweight or obese in the later study. One reason for a higher prevalence of obesity in ACHD patients could be that the issue of exercise is often not raised with ACHD patients. And if it is finally discussed, it is more common that patients receive prohibitive advice, leading to a more sedentary way of living. But in most ACHD patients exercise is safe, provided that individual exercise prescriptions are based on a comprehensive assessment of the underlying cardiac condition, possible sequelae, cardiac function, arrhythmias, pulmonary hypertension and aortic dimensions as well as individual exercise capacity. Recently published recommendations will hopefully lead to an improvement regarding this matter. A further cause for obesity discussed in ACHD patients is the encouragement of adequate nutrition as an early focus in the care of infants with CHD to catch up with their peers.
Smoking is associated with an increased risk for all types of cardiovascular disease—CAD and stroke to name a few—as well as a plethora of non-cardiovascular diseases like cancer. Fortunately, the proportion of ACHD patients that smoke has been reported to be smaller than in the general population. But if we consider the hazardous effects of smoking, it is worrisome that still between 13 and 23% of ACHD patients smoke.
Information regarding dyslipidemia in ACHD patients is scarce. Two large studies that assessed CVRF in ACHD patients did both not include data regarding lipid levels. One smaller study reported lower levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in ACHD patients in comparison to a general population sample group, while triglyceride levels were not different. In elderly patients with ACHD, the prevalence of dyslipidemia was reported to be 27%. In ACHD patients with established CAD, the prevalence of hyperlipidaemia is between 10 and 75% depending on the type of congenital heart defect.
Cardiovascular disease is the leading cause of morbidity and mortality in patients with diabetes mellitus. Two recent studies concordantly reported that approximately 3% of ACHD patients had diabetes. The prevalence was the same for ACHD patients and a control group without congenital heart disease.
In conclusion, all traditional CVRF associated with atherosclerotic disease are present in a substantial number of ACHD patients (Table 1).
Clinical Implications
The clinical picture of CAD in ACHD can be similar to that seen in the population without a congenital heart defect. In a study of 250 patients with ACHD that underwent coronary angiography for reasons other than suspected CAD, significant CAD was present in around 10% of these patients. The prevalence was similar to that in the general population. By means of CVRF, systemic arterial hypertension and hyperlipidaemia were strongly associated with CAD in this ACHD cohort. Interestingly, no patient with an age below 40 years had significant CAD. In contrast, Yalonetsky et al reported that in their study, 14% of ACHD patients with CAD had premature CAD (age <40 years). Therefore, even in ACHD patients below the age of 40 years, CAD cannot be ruled out. Systemic screening for ischaemic heart disease would probably reveal an even higher prevalence of CAD in ACHD. Therefore, as patients grew older, we have to expect a higher number of ACHD patients that are affected by CAD. This is not only of academic interest but comes along with a significant burden of morbidity and mortality. A recent study reported an almost threefold increase of percutaneous coronary interventions in a large sample of ACHD patients between 1998 and 2005. Furthermore, in a large registry study from the US myocardial infarction was the leading contributing cause of death in non-cyanotic ACHD patients. Additionally, in a study of ACHD patients beyond the age of 60, CAD was a strong prognostic factor on multivariate analysis and a key determinant of outcome in this elderly population in conjunction with the underlying congenital heart defect.
Risk of CAD in Selected Congenital Heart Defects
Cyanotic Congenital Heart Disease. It is often discussed that adults with cyanotic congenital heart disease may be protected from CAD because of protective antiatherosclerotic factors like hypocholesterolaemia, upregulation of nitric oxide, hyperbilirubinemia and others that are frequently encountered with cyanosis. And indeed, in the study by Giannakoulas et al none of the patients with cyanosis had significant CAD. In accordance, Fyfe and colleagues could not find obstructive CAD in any of their patients with cyanotic congenital heart disease. But we still have to be cautious since Yalonetsky et al reported in their study CAD in seven patients with Eisenmenger syndrome. Therefore, even adults with cyanotic congenital heart disease require surveillance for CAD.
Coarctation of the Aorta. Multiple studies have shown that the main cause of late death in patients with corrected coarctation of the aorta (CoA) is CAD. Furthermore, the life expectancy of patients with CoA—even after repair—is significantly reduced compared with the general population with premature cardiovascular death as the primary contributing factor to this worse outcome. Additionally, peripheral vascular disease and stroke have been reported to occur with a higher prevalence in patients with CoA compared with other ACHD patients in a study encompassing a large number of participants using administrative databases from Quebec. Interestingly, CoA alone did not predict CAD in the same study after adjusting for CVRF like arterial hypertension or hyperlipidaemia. It was concluded that CAD in CoA was mainly caused by the same traditional CVRF that predispose the general population to atherosclerotic disease. These CVRF had a much higher prevalence in CoA than in a control group of patients with ventricular septal defects. The important conclusion of this study is that it stresses the fact that the diagnosis of CoA itself is not a self-fulfilling prophecy of early cardiovascular death due to CAD. Careful targeting of traditional CVRF could possibly decrease the morbidity and mortality of this patient group.